Nucleosides, Nucleotides & Nucleic Acids最新文献

Colon cancer is a leading global malignancy with significant health burden. As key regulators of tumorigenesis, microRNAs (miRNAs) are implicated in colon cancer progression, yet the role of miR-1303-its clinical significance and molecular mechanism-remains unclear. This study aimed to investigate the regulatory effects of miR-1303 and validate its potential as an independent prognostic indicator. miR-1303 expression was analyzed via qRT-PCR in 117 paired CRC tissues and adjacent normal tissues. Clinical relevance was evaluated via Kaplan-Meier survival curves and Cox proportional hazards modeling. Functional assays (CCK-8, Transwell migration/invasion, luciferase reporter) were performed in SW480 and HCT116 cells. Target genes were predicted using miRDB and TargetScan. Rescue experiments confirmed miR-1303 regulates CRC progression by targeting TMEM108. miR-1303 was significantly upregulated in colon cancer tissues compared to normal tissues (p < 0.001) and correlated with advanced TNM stage (p = 0.021), lymph node metastasis (p = 0.005), poor differentiation (p = 0.031), and larger tumor size (p = 0.044). High miR-1303 expression predicted poorer overall survival (p = 0.001) and was recognized as an independent predictor of prognosis (HR = 2.096, 95% CI = 1.080-4.071). Functional studies revealed that miR-1303 inhibition suppressed colon cancer cell proliferation, migration, and invasion. Mechanistically, miR-1303 directly targeted the TMEM108, leading to its post-transcriptional repression. Upregulated miR-1303 in colon cancer served as a poor prognosis predictor. miR-1303 promotes tumor progression in colon cancer by targeting TMEM108.

Live-cell imaging of intracellular proteins enables real-time observation of protein dynamics under near-physiological conditions, providing pivotal insights for both fundamental life science research and medical applications. However, due to limitations such as poor probe permeability and cytotoxicity associated with conventional antibody-based or genetically encoded labeling techniques, live-cell imaging remains a significant challenging. To address these limitations, here in this study, we developed and rigorously validated a novel aptamer-based fluorescent probe for real-time imaging of NEK9 kinase in living cells. First, through in vitro capture-SELEX, a DNA aptamer termed as Apt-011 which could selectively bind NEK9 was identified. Further, capitalizing on the small size, low immunogenicity, and synthetic flexibility of aptamers, we engineered a "signal-on" NEK9-specific aptamer-based fluorescent probe platform. This design leverages the aptamer's target--induced conformational change to physically separate the fluorophore-quencher pair, and it has been validated that this fluorescent probe platform could successfully visualize intracellular NEK9 in live-cells without obvious cytotoxicity (cell viability > 95% at working concentrations), offering new opportunities to study NEK9-associated signaling pathways. This work not only provides a robust tool for kinase research but also establishes a generalizable strategy to overcome key bottlenecks in live-cell imaging through rational aptamer engineering.

Heart failure (HF) is not a disease but a combination of signs and symptoms caused by the failure of the heart to pump blood to support the circulatory system at rest or during activity. HF is the potential end stage of all heart diseases in which cardiomyopathies are a diverse group of cardiac disorders with distinct phenotypes, depending on the protein and pathways affected. Cardiomyopathies represent major causes of morbidity and mortality at all ages in humans in which hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), are the most common. Among the different common diagnostic tests for heart failure such as physical examination, blood tests, chest X-rays, electrocardiogram (ECG), etc. ultrasound has also been used not only for diagnosis such as echocardiography but also for therapeutic purposes. The development of therapeutic strategies for HF aiming to improve the heart's function, delay progression of HF, and treat HF symptoms as well as to stimulate the capacity to regenerate cardiomyocytes via stem cell therapy have been under intensive research interest. This narrative review aims to present the current understanding of the pathogenesis, diagnosis, and treatment of HF. Furthermore, as a perspective, this review navigates emerging therapies for HF by emphasizing on the use of low-intensity pulsed ultrasound (LIPUS) as a noninvasive therapy for (1) stimulation of the myocardial tissue reconstruction mechanisms; and (2) exploration of the molecular mechanisms behind the mechanotransduction from the muscle LIM protein (MLP), which is believed to be involved in human HF, using its expression vector via glycosylphosphatidylinositol, GPI, anchor.

Glioma represents the prevalent neoplasm type, distinguished by invasive growth and a significant rate of recurrence. This research investigates the prognostic significance and possible molecular mechanisms of miR-551a in gliomas, thereby offering a novel biomarker for gliomas treatment. This study selected 77 glioma patients and 52 craniocerebral injury patients from 2017 to 2023. The expression of miR-551a was assessed by qPCR. The ROC, Cox regression, and KM curve analyses were conducted to evaluate the diagnostic utility and prognostic value of miR-551a. The effects of inhibiting miR-551a on glioma cell functions were evaluated through CCK-8 and transwell assays. miR-551a target genes was conducted by GO and KEGG enrichment analyses, as well as PPI analysis, to elucidate potential gene regulatory relationship. miR-551a exhibited a significant up-regulation in the cerebrospinal fluid of glioma patients (P < 0.001). miR-551a possessed a robust predictive capacity for gliomas (AUC = 0.792, P < 0.001) and serves as a risk factor for unfavorable prognoses (HR = 3.858, P < 0.01), with patients exhibiting low levels of miR-551a showing favorable prognosis (P = 0.004). The inhibition of miR-551a diminished the proliferative (P < 0.05), migratory (P < 0.01), and invasive (P < 0.001) capabilities of glioma cells. miR-551a functioned as an oncogene, with CALM3 identified as critical regulatory targets (P < 0.001). miR-551a is a biological indicator for glioma prediction. It participates in the disease progression of glioma by regulating the functions of glioma cells via CALM3.

Four mixed ligand metal complexes have been synthesized from ortho-phenylenediamine (OPD) Schiff base and a dicarboxylic acid (succinic acid). Using spectral examinations in the UV-Vis, FT-IR, mass, electron paramagnetic resonance, and nuclear magnetic resonance, the prepared ligand and the complexes have been characterized. Numerous methodologies have been employed to examine pharmacological activities, including those related to anti-oxidant, anti-microbial, and DNA binding. Utilizing the B3LYP/6-31G (d) basis set and the Gaussian-09 program, the Density Functional theory investigations have optimized the ligand and its metal complexes' molecular structures in order to investigate the theoretical properties. Furthermore, all complexes involving the interacting amino acids of the bacterial kinase (PDB ID: 7VKB) and fungal kinase (PDB ID: 6U6A) underwent molecular docking studies. In the results, metal complex [CuL(L₁)] showed good DNA binding ability, antimicrobial (Lowest MIC 1.3 µg/mL), antifungal (Lowest MIC 1.2 µg/mL) and anioxidant (Lowest IC₅₀ 2.0 µg/mL) activities which ensure the good drug candidacy potentials of [CuL(L₁)].

Monocytes, upon activation, are known to produce substantial levels of cytokines and increased expression of MHC-I. The status of zinc and the nature of the stimulating agent significantly influence the release of various cytokines as well as the extent of MHC-I expression. However, research exploring the combined effects of inflammation and zinc deficiency remains limited. One of the primary challenges in investigating the influence of zinc status on cytokine production is the specificity of the cell types utilized in experimental settings. This study investigates zinc depletion and inflammation using THP-1 monocytes as an in vitro model, with HIV-1 viral peptide pools and TPEN (N,N,N' ,N'-Tetrakis (2-pyridylmethyl) ethylenediamine), an intracellular zinc chelator. Zinc depletion was confirmed through the application of zinquin ethyl ester via fluorescence microscopy. Additionally, we assessed the expression of zinc transporters, Bcl2 family proteins, and caspase-3 using quantitative RT-PCR and Western blot analyses. The production of TNF-α was evaluated through Golgi-Stop experiments, while MHC-I levels were measured following an 8 h incubation with HIV-1 viral peptides. The impact of PHA on monocytes concerning cytokine production and MHC-I levels was also examined. Our results revealed a rapid increase in TNF-α production and elevated MHC-I levels within 8 h post-stimulation. Furthermore, we observed an enhancement of endoplasmic reticulum (ER) stress markers, including CHOP, ATF6, and PERK, as well as BCl2 family-related genes, following treatment with the peptide pool. These findings highlight the hyperactivation of monocytes in response to HIV-1 viral peptides, which may contribute to immune system impairment through caspase-mediated apoptosis.

This review comprehensively examines nitrogen heterocyclic thioglycosides as promising therapeutic candidates for the development of antiviral drugs. Our aim is to explore recent advancements and the therapeutic potential of their analogues. By integrating knowledge from diverse fields, we seek to understand how these compounds can be leveraged to create effective and targeted antiviral therapies. Our findings underscore the significant potential of nitrogen heterocyclic thioglycosides as viable options for future antiviral drug development, emphasizing their ability to specifically engage and modulate key pathways. This study concludes by highlighting the crucial role of these compounds in medicinal chemistry and their promise in contributing to the creation of novel and potent antiviral agents.

In the present study, we investigated the relationship between rheumatoid arthritis (RA) and knee osteoarthritis (OA) using bioinformatics, aiming to identify the differentially expressed genes (DEGs) of RA and explore the possible mechanism of RA. The GSE55584 and GSE153015 microarray datasets for RA and OA gene expression profiles were acquired from the Gene Expression Omnibus (GEO) database. The DEGs of the two datasets were obtained by R language processing and analysis. The intersecting DEGs were obtained using the Venny 2.1 platform. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genome (KEGG) enrichment analyses were performed using the DAVID platform, and the microbubble map was drawn online by importing the microbubble generation platform. All the obtained DEGs and the intersecting DEGs were imported into the STRING platform to obtain a protein-protein interaction network (PPI) and then into Cytoscape 3.9.1 software to screen core genes (hub genes). A total of 665 DEGs were obtained from the GSE55584 and GSE153015 datasets, including 324 upregulated and 341 downregulated DEGs. GO enrichment analysis showed that the biological processes in which DEGs were mainly enriched included signal transduction, immune response, inflammatory response, adaptive immune response, and G protein-coupled receptor signalling pathway. KEGG enrichment analysis of the DEGs identified the following enriched pathways: cytokine-cytokine receptor interaction; chemokine signalling pathway; viral protein interaction with cytokines and cytokine receptors; and apoptosis. Ten core genes (hub genes) were screened out, namely, CD3D, CD27, KLRB1, CCL5, GZMB, GZMA, GZMK, GNLY, CD2, and NKG7. Among them, CD3D, CD27, KLRB1, CCL5, and GZMB were most significantly correlated with the occurrence and development of RA. In the present study, bioinformatics analysis provided supporting evidence for the biological process and key genes of RA.

Transcription factors (TFs) play a crucial role in tumorigenesis by driving oncogene expression in key signaling pathways. However, their small size and flat surfaces make them challenging targets for small-molecule inhibitors, while macromolecular therapies struggle to cross the cell membrane. Modulating TF activity at the genetic level offers a promising alternative. Antisense oligonucleotides (ASOs), which regulate protein expression by targeting mRNA, have emerged as effective therapeutics for previously undruggable proteins, including TFs. Over the past two decades, ASO therapeutics have advanced significantly, demonstrating long-lasting efficacy by promoting mRNA degradation. c-Myc, a key regulator of oncogene expression, drives cancer cell growth and proliferation but remains undruggable due to its nuclear localization and dynamic structure. In this study, we utilized our ASO development platform to design ASOs targeting c-Myc. Our sequence optimization algorithm achieved high accuracy, with one of three designed ASOs successfully silencing c-Myc. Ex vivo validation showed that ASO3 inhibited A549 cell growth with an IC₅₀ of 152.5 nM. At the molecular level, ASO3 significantly reduced both c-Myc mRNA and protein expression. Functional assays, including trypan blue exclusion assay and CCK-8, confirmed that ASO3 decreased cell viability, suppressed proliferation, and induced apoptosis. These findings highlight ASO3's therapeutic potential and support further investigation as an anti-cancer agent targeting c-Myc.

Several studies have shown the role of circRNAs in tumor cell proliferation, migration, invasion, apoptosis, angiogenesis, and recurrence, suggesting potential as a biological marker and target for therapy for preventing and therapeutic management of cancer. This systematic review summarizes the role of circRNA on OC signaling networks and reveals potential oral cancer (OC) treatment targets. The systematic review followed PRISMA guidelines for study selection, synthesis, and dissemination. PubMed, Scopus, and Web of Sciences were searched for evidence-based studies on circRNA on OC from January 2015 to December 2024. Two experts performed an unbiased inquiry and specified screening. The Cochrane Collaboration tool assessed the risk of bias (RoB) using ROBINS-I, which classifies bias as low, moderate, serious, critical, or no information. The systematic review comprised 19 papers. High-throughput sequencing techniques or circRNA microarray studies for OSCC revealed numerous differentially expressed circRNAs across OSCC tissues and neighboring tissues. Subsequently, a series of studies demonstrated that certain circRNAs serve pivotal roles in the genesis and progression of OC. Many circRNAs are essential regulators of pivotal pathways in oral malignancies. CircRNAs work by competitively binding or "sponging" miRs through the development of persistent complementary contacts, RNA-binding protein sponges, protein/peptide translators, and regulators of gene splicing and transcription.